Hedgehog Drug Development Services

Alfa Cytology specializes in Hedgehog (Hh) signaling pathway drug development. We provide tailored solutions for the design, development, and characterization of Hh inhibitors. Leveraging deep expertise in drug discovery, our comprehensive services support your entire research and development pipeline targeting this pathway.

Introduction to Hedgehog Pathway

The Hedgehog (Hh) signaling pathway is a critical regulator of embryonic development and tissue homeostasis. Initially discovered through its role in embryonic segmentation in Drosophila (fruit flies), the pathway derives its name from the Hedgehog protein. Dysregulation or aberrant activation of Hh signaling is implicated in the pathogenesis of multiple cancers, including leukemia. Such hyperactivity drives uncontrolled cell proliferation and survival, which can contribute to therapy resistance.

Fig. 1. Simplified overview of the Hh signaling pathway in the (A) inactive state and (B) active state. (Jamieson, C. et al., 2020)

We design inhibitors targeting Smoothened (SMO) and glioma-associated oncogene homolog (GLI), based on their structure, and develop key targets for new drugs to treat malignant tumors, including acute myeloid leukemia.

SMO Inhibitors

• Design and Synthesis
  We will design and synthesize alkaloid cyclopamine based on its structure. Moreover, efforts will be made to optimize the structure of the cyclopamine derivatives for increased specificity, potency, and solubility, thereby making them candidates for clinical trials.
• Drug Screen
  Using our development systems and available screening methods, we are capable of screening a large number of compound libraries against alkaloid cyclopamine in search of novel SMO antagonists. We would then be able to establish further capabilities and conduct functional optimization of these antagonists toward their extended use.
• Combination Therapy
  Compared to monotherapy, the combination of glasdegib with chemotherapy demonstrates better clinical activity in treating acute myeloid leukemia. We possess significant experience with the development of methodologies to combine glasdegib with chemotherapy, enabling you to investigate optimal chemotherapy drug combinations.
• Addressing Drug Resistance
  Our service in glasdegib and chemotherapy combination development will offer great insight into resisting such SMO inhibitors in specific tumor types.

GLI Inhibitors

Evaluation of Hedgehog Pathway Inhibitors

Comprehensive analyses can be done to study the efficacy of Hedgehog pathway inhibitors and further examine substantial potential at later development stages.

Driven by a commitment to purpose-driven innovation, Alfa Cytology delivers high-quality drug development services focused on Hedgehog (Hh) signaling pathway inhibitors. Our specialized approach advances novel therapies for acute myeloid leukemia (AML) and other hematopoietic-origin malignancies. Contact us to discuss how our targeted inhibitor development services can accelerate your oncology research.